PXD014474

PXD014474 is an original dataset announced via ProteomeXchange.

Title	A targeted strategy for developing proteomic biomarkers: a case study of epithelial ovarian cancer
Description	Protein biomarkers for epithelial ovarian cancer are critical for the early detection of the cancer to improve patient prognosis and for the clinical management of the disease to monitor treatment response and to detect recurrences. Unfortunately, the discovery of protein biomarkers is hampered by the limited availability of reliable and sensitive assays needed for the reproducible quantification of proteins in complex biological matrices such as blood plasma. In recent years, targeted mass spectrometry, exemplified by Selected Reaction Monitoring (SRM) has emerged as a method, capable of overcoming this limitation. Here, we present a comprehensive SRM-based strategy for developing plasma-based protein biomarkers for epithelial ovarian cancer and illustrate how the SRM platform, when combined with rigorous experimental design and statistical analysis, can result in detection of predictive analytes. Our biomarker development strategy first involved a discovery-driven proteomic effort to derive potential N-glycoprotein biomarker candidates for plasma-based detection of human ovarian cancer from a genetically engineered mouse model of endometrioid ovarian cancer, which accurately recapitulates the human disease. Next, 65 candidate markers selected from proteins of different abundance in the discovery dataset were reproducibly quantified with SRM assays across a large cohort of over 200 plasma samples from ovarian cancer patients and healthy controls. Finally, these measurements were used to derive a 5-protein signature for distinguishing individuals with epithelial ovarian cancer from healthy controls. The sensitivity of the candidate biomarker signature in combination with CA125 ELISA-based measurements currently used in clinic, exceeded that of CA125 ELISA-based measurements alone. The SRM-based strategy in this study is broadly applicable. It can be used in any study that requires accurate and reproducible quantification of selected proteins in a high-throughput and multiplexed fashion.
HostingRepository	PanoramaPublic
AnnounceDate	2019-08-14
AnnouncementXML	Submission_2019-08-14_15:16:48.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Ruth Huttenhain
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	Carbamidomethyl; Label:13C(6)15N(2); Label:13C(6)15N(4)
Instrument	TSQ Vantage; QTRAP 5500; 4000 QTRAP

Revision	Datetime	Status	ChangeLog Entry
0	2019-07-03 06:48:45	ID requested
⏵ 1	2019-08-14 15:16:57	announced

H, ü, ttenhain R, Choi M, Martin de la Fuente L, Oehl K, Chang CY, Zimmermann AK, Malander S, Olsson H, Surinova S, Clough T, Heinzelmann-Schwarz V, Wild PJ, Dinulescu DM, Nim, é, us E, Vitek O, Aebersold R, A Targeted Mass Spectrometry Strategy for Developing Proteomic Biomarkers: A Case Study of Epithelial Ovarian Cancer. Mol Cell Proteomics, 18(9):1836-1850(2019) [pubmed]

submitter keyword: Cancer biomarker, Ovarian cancer, Plasma

Ruth Huttenhain
contact affiliation	Department of Cellular & Molecular Pharmacology, UCSF
contact email	ruth.huttenhain@ucsf.edu
lab head
Ruth Huttenhain
contact affiliation	Department of Cellular & Molecular Pharmacology, UCSF
contact email	ruth.huttenhain@ucsf.edu
dataset submitter

Panorama Public dataset URI